The Long-term effects on antenatal glucocorticoids and preterm birth

Abstract

Antenatal glucocorticoids are widely used in perinatal medicine, and are one of the key treatments responsible for improving survival of preterm infants since the 1960s. A systematic review reported in this thesis concludes that antenatal glucocorticoids reduce the risk of neonatal death, respiratory distress syndrome (RDS), intraventricular haemorrhage, necrotising enterocolitis, infectious morbidity and need for respiratory support. Several areas of uncertainty have been clarified, including the effectiveness of treatment in the current era of neonatal practice, and in women with hypertension syndromes and premature rupture of membranes. However there is a paucity of data on long-term outcomes after exposure to antenatal glucocorticoids. This is particularly important given recent proposals that fetal exposure to excess glucocorticoids may be a core mechanism explaining the epidemiological evidence that those born small are at increased risk of later adult disease. Furthermore, the relative contributions of fetal growth and prematurity to small size at birth, and hence later disease risk, has not been well elucidated. This thesis reports the follow-up of 534 thirty year olds whose mothers participated in the first, and largest, randomised trial of antenatal betamethasone for prevention of neonatal RDS. Two-thirds of participants were born preterm. Follow-up assessments included cardiovascular risk factors, spirometry, psychological assessment and bone densitometry. Exposure to antenatal betamethasone did not affect mortality, body size, blood pressure, lung function, fasting plasma levels of lipids, cortisol or IgE, socio-economic status, psychological functioning, health related quality of life or bone mass. However betamethasone-exposed participants showed increased insulin resistance. This is the first experimental evidence in man to demonstrate long-term metabolic effects of fetal glucocorticoid exposure. However, as all other outcomes are reassuring, and treatment significantly reduces neonatal mortality and morbidity, obstetricians should continue to use a single course of glucocorticoids for the prevention of neonatal RDS. Adults who were born preterm had increased blood pressure, insulin resistance, reduced lung function and reduced adult height at age thirty. This is the largest reported follow-up of ex-preterm infants into adulthood. Although the associations are relatively small, their potential implications for the prevalence of later chronic obstructive pulmonary and cardiovascular disease are of concern.